Active agents are commonly administered to a subject parenterally either by injection or infusion. The commonly used distinction between the two is that an injection introduces a dosage of drug in a pulse form, either subcutaneously, intramuscularly, intravenously, or intraarterially, whereas an infusion introduces the active agent in a continuous manner over a prolonged period of time, such as, for example, in the conventional intravenous drip.
It is known to the art that it is generally more desirable to eliminate pulse dosages in which a relatively large amount of the active agent is rapidly deposited for consumption in the body over a prolonged period of time, in favor of the administration over long periods of time of smaller doses. See, for example, Therapeutic Systems, Pattern Specific Drug Delivery, Concept and Development, Klaus Heilman, George Thieme Publishers, Stuttgart, 1978.
Until recently the only manner by which certain active agents could be delivered in this fashion was through intravenous administration which required that a subject be connected to an intravenous drip apparatus. This required immobilization and sometimes hospitalization of the subject. Recently various devices have been developed of which U.S. Pat. No. 3,895,631 Buckles, et al., July 22, 1975, Liquid Infusion Unit, is representative, which permit the ambulatory administration of intravenous medications. Thus a subject is now freed to lead a relatively normal life while the liquid infusion unit is worn by the patient and delivers a relatively constant amount of active agent over prolonged periods of time. The devices have been quite useful; however, this particular type of device which is powered by an elastomeric bladder, has been designed to dispense relatively large amounts of fluid (in the order of 40-60 milliliters) and is not particularly adaptable to the prolonged administration of small amounts of active agents, especially highly potent or expensive drugs, on the order of less than 10 milliliters. An osmotically activated infusor device for smaller quantities is disclosed in the copending patent application of Benjamin J. Eckenhoff, Ser. No. 246,595 filed Mar. 28, 1981 for Self Driven Hypodermic Injection.
There currently exist devices, which are actuated upon the exposure to a fluid environment, such as the ALZET.RTM. miniosmotic pumps and OROS.RTM. elementary osmotic pumps available from ALZA Corporation, 950 Page Mill Road, Palo Alto, Calif. 94304 which are designed to release small amounts of materials over prolonged periods of time. For example, ALZET mini-osmotic pumps are available which will release 200.mu. liters of fluid at the rate of 0.5.mu. liters per hour for 2 weeks or 1.mu. liter per hour for one week. Others have been produced which release 2 ml of fluid over the same time periods. Such devices are compact and have overall dimensions as small as 3 centimeters in length and 0.7 centimeters in diameter. Similar devices actuated upon exposure to a fluid environment are disclosed in U.S. Pat. Nos. 3,995,631, 3,845,770, 3,916,899, 3,987,790, 3,760,984, 3,760,804, 4,203,440, 4,016,880, 4,111,202, 4,111,203, 4,203,442, and 4,210,139 for example which are incorporated herein by reference. Although there are differences in structure and details of operations, the term "fluid imbibing pump" as used herein encompasses all such devices and is intended to include any dispensing device which is caused to expel its contents over an extended period of time upon immersion in a fluid. In operation, these devices are implanted within the body of the subject or are ingested or otherwise introduced into the G.I. tract and are actuated by the imbibition of liquid, i.e., water, from the body inwardly through the permeable or semipermeable membrane creating a pressure differential sufficient to expel the fluid contents of the pump through an outlet orifice at a constant rate throughout the operation of the device. Such devices are particularly useful in experimental and therapeutic administration of active agents to humans and animals, but they are dependent on the body fluids for activation and have not been applied externally. In addition, the flow rate of these devices is predetermined and variations including stopping and restarting after start up are not easily achieved. According to this invention, a lightweight, compact, inexpensive, self-contained externally mounted pump which is capable of dispensing a relatively small amount of liquid over a prolonged period of time is provided. In addition, in certain embodiments of this invention, means are provided by which this basal or tonic dispensing rate can be varied.
It is accordingly an object of this invention to provide a self-contained, externally mounted pump particularly useful for introducing small amounts of an active agent into a subject over a prolonged period of time.
It is another object of this invention to provide a pump in which the flow rate may be varied, including being stopped and restarted.
It is another object of this invention to provide a self-powered infusor which is capable of operating with existing fluid imbibing pumps.